Ultrasensitive test detects protein clumps to diagnose rare dementia subtype

Dementia affects over 57 million people worldwide, a number expected to nearly double in the next 20 years. This permanent loss of cognitive abilities affects daily function and can be caused by multiple brain pathologies, including well known ones like Alzheimer's disease (AD). Right now, biomarkers permit diagnosis of AD but not rarer pathologies like frontotemporal lobar degeneration (FTLD) or its subtypes. Investigators from Mass General Brigham developed an ultrasensitive test capable of detecting abnormal clumps of a protein called TDP-43, which defines a specific subtype of FTLD pathology called FTLD-TDP.

Findings, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, could help better diagnose dementia patients with the correct pathology, improving research and drug development.

"In this study, we found elevated concentrations of a biomarker that correlates with FTLD-TDP disease severity," said co-senior author David R. Walt, PhD, of the Mass General Brigham Department of Pathology. Walt is also a core faculty member of the Wyss Institute at Harvard University, associate member at the Broad Institute, and a Howard Hughes Medical Institute professor. "This is just a first step, but it's an important one because it gives us something measurable. Our vision is to create a test to diagnose patients, monitor treatment efficacy in clinical trials, and follow patient progression."

Much more work is needed to validate this test rigorously, but this study establishes a framework for developing better tools for diagnosing this devastating disease and monitoring molecular pathology among patients with FTLD. Our test is one of several in development across the world which show promise in eventually giving FTD patients an accurate diagnosis, which is necessary for developing an accurate treatment."